Abstract and Introduction

Abstract

Signs of motor dysfunction are evidenced across a range of psychiatric disorders including schizophrenia. Historically, these features have been neglected but emerging theoretical and methodological advancements have shed new light on the utility of considering movement abnormalities. Indeed, the National Institute of Mental Health Research Domain Criteria initiative has recently met to develop a Motor Systems Domain. This reflects a growing appreciation for the enhanced reliability and validity that can come along with evaluating disturbances relevant to psychiatric illnesses from multiple levels of analysis, and conceptualizing these domains with respect to the complexity of their role in a broader integrated system (ie, weighing contributions and interactions between the cognitive, affective, and motor domains). This article discusses motor behaviors and seeks to explain how research into basal ganglia, cerebellar, and cortico-motor circuit function/dysfunction, grounded in brain circuit-motor behavior relationships, can elucidate our understanding of pathophysiology, provide vital links to other key systems of interest, significantly improve identification and classification, and drive development of targeted individualized treatments.

Introduction

Psychiatric disorders like psychosis and bipolar disorder (BD) show cognitive, social, affective, sensory, thought and motor symptoms. While significant attention has been devoted to cognitive and affective symptoms, motor changes are often neglected. This phenomenon, as well as the rich history of research into motor dysfunction across psychiatric illnesses, is discussed comprehensively in Peralta and Cuesta's review (this issue). Until recently, such neglect has gone along with limited integration with research supporting the contribution of the underlying basal ganglia, cerebello-thalamo-cortical and cortico-motor circuits involved in the various aspects of motor function such as excitation/inhibition, timing, and psychomotor modulation (Figure 1). The aim in the present paper is to show the relevance of these 3 circuits for different aspects of "normal" motor function and their neural-behavioral-motor alterations in psychosis.

The figure shows the relevant motor circuits for psychosis. (A) Basal ganglia circuit. GPi and e: Globus pallidus internal and external; STN = subthalamic nucleus. (B) Cerbellar-thalamo-cortical circuit. Here, we show the cerebello-thalamo-motor. While the cerebello-thalamo-frontal circuit was originally noted by Andreasen and colleagues28 as being implicated in patients with schizophrenia, more recent work, including our own, has demonstrated that the cerebello-thalamo-motor circuit is also impacted in this population, and relates to deficits in sensorimotor integration. (C) Cortico-motor circuits. Multiple areas of the frontal and parietal cortices interact to control and influence movement. Notably, these regions also interact with the subcortical systems in (A) and (B).

Further underscoring the potential importance of motor symptoms in psychosis, and across psychopathology more broadly, is the new addition of the Motor Systems domain to the National Institute of Mental Health Research Domain Criteria (RDoC) matrix. A primary goal of the RDoC framework is to shift psychopathology research towards a pathophysiology-based framework.[1,2] Just as in other RDoC matrix domains, the Motor Systems domain is comprised of multiple constructs and subconstructs meant to guide research in this area from the cellular-molecular level, up to observable behavior and reports, including brain-circuit based measures (see editorial by Garvey and Cuthbert in this issue). As we put the function of key motor circuits into context, we do so with an eye towards the RDoC matrix, and describe how investigations of these circuits in psychotic disorders may be especially informative for our understanding of the disease.

The figure shows the relevant motor circuits for psychosis. (A) Basal ganglia circuit. GPi and e: Globus pallidus internal and external; STN = subthalamic nucleus. (B) Cerbellar-thalamo-cortical circuit. Here, we show the cerebello-thalamo-motor. While the cerebello-thalamo-frontal circuit was originally noted by Andreasen and colleagues28 as being implicated in patients with schizophrenia, more recent work, including our own, has demonstrated that the cerebello-thalamo-motor circuit is also impacted in this population, and relates to deficits in sensorimotor integration. (C) Cortico-motor circuits. Multiple areas of the frontal and parietal cortices interact to control and influence movement. Notably, these regions also interact with the subcortical systems in (A) and (B).